Project Summary/Abstract The Boston University (BU) Department of Chemistry seeks NIH support to acquire a Thermo Scientific Orbitrap Fusion Lumos Tribrid Mass Spectrometer (Fusion Lumos) for its Charles River Campus (CRC). This instrument would enable investigators on the CRC and collaborators to advance research in chemical biology and move into new areas that enrich student and postdoctoral training. In particular, the instrument?s unique and flexible capabilities would enhance active research projects focusing on determining the molecular targets (mechanism of action) of bioactive small molecules using innovative liquid chromatography mass spectrometry (LC/MS) techniques. These include target identification by Ligand Stabilization/Thermal Profiling, Affinity Capture, and other chemical-proteomic methods that depend on precision LC/MS to obtain accurate quantitative and qualitative information on the direct binding targets of bioactive compounds of interest to researchers in the departments of Chemistry, Biochemistry, Biology, Biomedical Engineering, School of Medicine at BU, collaborators at Massachusetts Institute of Technology and in the pharmaceutical industry. Acquisition of this instrument is critical to the research programs of a number of Major Users (Professors Beeler, Brown, Cheah, Hansen, Harris, Koehler, Kotton, Kramnik, Liu, Porco, Schaus, Vegas, Whitty and Wolozin), Minor Users (Professors Connor, Elliott and Feng), one group in the pharmaceutical industry, as well as other potential collaborators. The requested instrument will also play a pivotal role in a joint research platform, the Target Discovery Laboratory (TDL), developed by Professors Emili and Porco in 2017. The University?s commitment is demonstrated by its investment in the infrastructure for multi-user research instruments and by its provision of partial salary support for five years totaling $280,000 for the expert TDL LC/MS spectrometrist (Dr. Mark McComb) as well as support towards the instrument?s service contract ($111,035). TDL faculty, along with Dr. Norman Lee from the Chemistry Chemical Instrumentation Center (CIC) will direct and supervise use of the instrument while the maintenance, operations and training will rest with Dr. McComb. The training of young scientists in the use and interpretation of precision mass spectrometry and chemical proteomics will not only facilitate their own research objectives, but will also provide valuable additional technical knowledge and skills for successful future careers in academia, government and industry.